What vibrations tell us about proteins

This review deals with current concepts of vibrational spectroscopy for the investigation of protein structure and function. While the focus is on infrared (IR) spectroscopy, some of the general aspects also apply to Raman spectroscopy. Special emphasis is on the amide I vibration of the polypeptide backbone that is used for secondary-structure analysis. Theoretical as well as experimental aspects are covered including transition dipole coupling. Further topics are discussed, namely the absorption of amino-acid side-chains, 1H/2H exchange to study the conformational flexibility and reaction-induced difference spectroscopy for the investigation of reaction mechanisms with a focus on interpretation tools.     

What does halobacterium tell us about photoreception?

European Biophysics Journal -     

What does Halobacterium tell us about photoreception?

A photosensory mechanism is proposed for Halobacterium halobium based on the observation of light-induced motor responses. Possible mechanisms of signal transduction in Halobacterium are discussed. Bacteriorhodopsin and the visual pigment rhodopsin are compared with respect to their structural and functional properties. The conclusion is drawn that Halobacterium may help to understand primary photochemical events of rhodopsin rather than the transduction mechanism of visual photoreceptors.Presented at the EMBO-Workshop on Transduction Mechanism of Photoreceptors, Jülich, Germany, October 4–8, 1976     

What transgenic mice tell us about neurodegenerative disease

The recent broad advance in our understanding of human neurodegenerative diseases is based on the application of a new molecular approach. Through linkage analysis, the genes responsible for Huntington's disease, the spinocerebellar ataxias, and familial forms of Alzheimer's disease and amyotrophic lateral sclerosis (ALS) have been identified and cloned. The characterization of pathogenic mutations in such genes allows the creation of informative transgenic mouse models as, without exception, the genetic forms of adult neurodegenerative disease are due to toxicity of the mutant protein. Transgenic models provide insight into the oxidative mechanisms in ALS pathogenesis, the pathogenicity of expanded polyglutamine tracts in CAG triplet repeat disorders, and amyloidogenesis in Alzheimer's disease. Although such models have their limitations, they currently provide the best entry point for the study of human neurodegenerative diseases.     

What systems biology can tell us about disease

A recent debate has touched upon the question of whether diseases can be understood as dysfunctional mechanisms or whether there are "pathological" mechanisms that deserve to be investigated and explained independently (Nervi 2010; Moghaddam-Taaheri 2011). Here I suggest that both views tell us something important about disease but that in many instances only a systemic view can shed light on the relationship between physiology and pathology. I provide examples from the literature in systems biology in support of my position. As a result of my analysis, I conclude that a perspective narrowly focusing on mechanisms is insufficient if the goal is to get a comprehensive picture of disease.     

What primary microcephaly can tell us about brain growth

Autosomal recessive primary microcephaly (MCPH) is a neuro-developmental disorder that causes a great reduction in brain growth in utero. MCPH is hypothesized to be a primary disorder of neurogenic mitosis, leading to reduced neuron number. Hence, MCPH proteins are likely to be important components of cellular pathways regulating human brain size. At least six genes can cause this disorder and four of these have recently been identified: autosomal recessive primary microcephaly 1 (MCPH1), abnormal spindle-like, microcephaly associated (ASPM), cyclin-dependent kinase 5 regulatory subunit-associated protein 2 (CDK5RAP2) and centromere protein J (CENPJ). Whereas aberration of ASPM is the most common cause of MCPH, MCPH1 patients can be more readily diagnosed by the finding of increased numbers of "prophase-like cells" on routine cytogenetic investigation. Three MCPH proteins are centrosomal components but have apparently diverse roles that affect mitosis. There is accumulating evidence that evolutionary changes to the MCPH genes have contributed to the large brain size seen in primates, particularly humans. The aim of this article is to review what has been learnt about the rare condition primary microcephaly and the information this provides about normal brain growth.     

What can two-dimensional NMR tell us about proteins?

As a result of spectacular advances in recent years, nuclear magnetic resonance (NMR) is now firmly established as an essential tool in protein research, providing both a unique method for three-dimensional structure determination and powerful new approaches for studies of protein dynamics and folding.     

What do mathematical models tell us about circadian clocks?

The paper reviews a series of models for circadian clocks and discusses their conclusions and predictions. Attention is focused on Pittendrigh's empirical model, two mathematical models by the author and Winfree's work.     

What tubulin drugs tell us about microtubule structure and dynamics

A wide range of small molecules, including alkaloids, macrolides and peptides, bind to tubulin and disturb microtubule assembly dynamics. Some agents inhibit assembly, others inhibit disassembly. The binding sites of drugs that stabilize microtubules are discussed in relation to the properties of microtubule associated proteins. The activities of assembly inhibitors are discussed in relation to different nucleotide states of tubulin family protein structures.     

What canCaenorhabditis elegans tell us about nematocides and parasites?

Nematode infections compromise human health and reduce agricultural productivity. Experiments that exploit the powerful molecular genetics of the free-living nematodeCaenorhabditis elegans have contributed to our understanding of how the major classes of anthelmintic nematocides kill worms and how worms might evolve resistance to these drugs. InC. elegans, as in parasites, benzimidizoles interfere with microtubule polymerization, the imidazothiazoles/tetrahydropyrimidines activate nicotinic acetylcholine receptors, and the macrocyclic lactones activate glutamate-gated chloride channels. Mutant alleles of genes that encode drug targets often confer resistance inC. elegans. Preliminary evidence suggests that alleles of homologous genes in parasites will, in many cases, also play a role in resistance. Thus, information acquired fromC. elegans can be usefully applied to understand the mechanisms of drug sensitivity and the genetics of resistance in parasites.     

Double impact: What sibling data can tell us about the long‐term negative effects of parental divorce

Abstract

Most prior research on the adverse consequences of parental divorce has analyzed only one child per family. As a result, it is not known whether the same divorce affects siblings differently. We address this issue by analyzing paired sibling data from the 1994 General Social Survey (GSS) and 1994 Survey of American Families (SAF). Both seemingly unrelated regressions and random effects models are used to study the effect of family background on offspring's educational attainment and marital stability. Parental divorce adversely affects the educational attainment and the probability of divorce of both children within a sibship; in other words, siblings tend to experience the same divorce the same way. However, family structure of origin only accounts for a trivial portion of the shared variance in offspring's educational attainment and marital stability, so parental divorce is only one of many factors determining how offspring fare. These findings were unchanged when controlling for a number of differences both between and within sibships. Also, the negative effects of parental divorce largely do not vary according to respondent characteristics.